# The epigenetics of exercise and physical activity in COPD

> **NIH VA IK2** · VA BOSTON HEALTH CARE SYSTEM · 2020 · —

## Abstract

Chronic obstructive pulmonary disease (COPD) is highly prevalent among U.S. Veterans and is a significant
source of morbidity and mortality. Patients with COPD frequently have reduced exercise capacity (defined
as a patient's maximal capacity to perform work) and levels of physical activity (a term frequently used to
describe a patient's typical daily level of activity). Reduced exercise capacity and physical activity are
correlated with significant clinical outcomes, such as disability, all-cause mortality, and healthcare utilization
rates. Importantly, exercise capacity and physical activity represent potentially modifiable risk factors in
COPD. Exercise training, which is typically performed in the setting of a structured pulmonary rehabilitation
program, is currently endorsed by the Global Initiative for Obstructive Lung Diseases (GOLD) guidelines as
an essential component of the non-pharmacological management of COPD and has been shown to improve
symptoms and health-related quality of life while reducing healthcare utilization. In addition to formal
pulmonary rehabilitation, novel programs which focus on improving daily physical activity may provide
similar benefits. In addition to the disease-specific benefits above, exercise training and increased physical
activity have also been associated with systemic changes such as improved macronutrient metabolism,
increased muscle mass, and decreased systemic inflammation. However, COPD patients vary widely in
their responses to exercise interventions. Our understanding of the mechanisms which determine exercise
capacity and the response to training is incomplete; our hypothesis is that epigenetic mechanisms such as
DNA methylation are associated with both baseline exercise capacity and the systemic reprogramming that
occurs with training. We propose to examine genome-wide DNA methylation patterns in blood from 2
existing VA-Boston based cohorts of COPD subjects with detailed, objective data on both exercise capacity
and daily physical activity. Analysis of the first cohort, a cross-sectional cohort which includes subjects with
a broad range of functional limitation, will help to establish the epigenetic determinants of baseline exercise
capacity and physical activity (Objective 1). In the second cohort, we will determine longitudinal changes in
methylation following an intervention to increase daily physical activity using paired samples collected
before and after participation in the Every Step Counts trial (Objective 2). Finally, because traditional
pulmonary rehabilitation programs typically involve higher intensity training than programs which target daily
physical activity (such as the Every Step Counts program), we propose to collect de novo samples from
COPD subjects referred to the VA Boston Pulmonary Rehabilitation program to characterize changes
associated with higher intensity training (Objective 3). In addition to providing mechanistic insights on the
benefits of exercise and increased ...

## Key facts

- **NIH application ID:** 9989675
- **Project number:** 5IK2RX002165-05
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** Emily S Wan
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2016-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989675

## Citation

> US National Institutes of Health, RePORTER application 9989675, The epigenetics of exercise and physical activity in COPD (5IK2RX002165-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9989675. Licensed CC0.

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